The focus of this grant is on tumors of the central nervous system with the goal of defining mechanisms responsible for their growth. This focus on CNS tumors makes the project more difficult than a focus on tumors in general. However, the fragmentary knowledge available on the molecular biology of CNS tumors along with the absence of any effective therapy for the malignant astrocytoma, the most common tumor, are two major reasons for the restricted focus. The hope is that mechanistic knowledge will eventually lead to new therapeutic approaches. To discover oncogenes active in CNS tumors we are devising an assay as an alternative to that with the NIH 3T3 cell. Two growth factor related systems, the platelet derived growth factor (PDGF) and the epidermal growth factor (EGF) systems, have been identified by others, as involved in CNS tumors. We are doing detailed studies on the expression of the sis gene (PDGF-B). Finally we shall examine the expression of a series of oncogenes in glioblastomas as well as evaluate autocrine regulation in these tumors.